The studies reported by this grant have investigated and quantitated injury of a model gastric mucosa by weak acid analgesics (aspirin, salicylic acid, phenylbutazone, and indomethacin). The studies have been extended into investigating interaction of these agents with purified cell membranes obtained by density gradient centrifugation. The studies have shown that fluorescence techniques using aspirin and salicylic acid are inadequate probes of membrane interaction. Anilino naphthalene sulfonic acid (ANS) has at least two binding sites; one of these predominates at low pHs. ANS was also found to inhibit the gastric K+ ATPase which is thought to be related to acid secretion. Studies of adenosine triphosphatate (ATP) and phosphocreatine (PC) content of control and injured mucosae shows that ATP and PC content is reduced following ASA injury and that the reduction is more marked with prolonging exposure. In addition ASA was found to inhibit H+ secretion and C1- transport by gastric mucosa and to increase permeability of the mucosa to mannitol. 02 consumption is increased in the early phases of ASA injury. Initial studies of human gastric biopsies have revealed a reduction of ATP and PC content upon ASA treatment. Thus in these preliminary studies injury of human gastric mucosa conforms well to findings using the amphibian mucosa. BIBLIOGRAPHIC REFERENCES: Spenney, J.G. and F. Ostroy. An Adjustable constant current stimulator for electrode physiologic experiments. Institute of Electrical and Electronics Engineers, Inc. Transactions. In press, 1976. Rabon, E., J.G. Spenney, W.S. Rehm and G. Sachs. Characterization of gastric mucosal membranes. IX. The action of histamine and burimamide on the gastric muscosal redox components. Proc. N.Y. Acad. Sci. In press, 1976.